Please use this identifier to cite or link to this item: https://dora.health.qld.gov.au/qldresearchjspui/handle/1/2536
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dc.contributor.authorMcKee, S. A.en
dc.contributor.authorChen, W.en
dc.contributor.authorAnderson, G.en
dc.contributor.authorMorrogh, D.en
dc.contributor.authorMoulding, D. A.en
dc.contributor.authorNiemeyer, C. M.en
dc.contributor.authorAchermann, J. C.en
dc.contributor.authorGrÜTers, A.en
dc.contributor.authorBuonocore, F.en
dc.contributor.authorKÜHnen, P.en
dc.contributor.authorSuntharalingham, J. P.en
dc.contributor.authorDel Valle, I.en
dc.contributor.authorDigweed, M.en
dc.contributor.authorStachelscheid, H.en
dc.contributor.authorKhajavi, N.en
dc.contributor.authorDidi, M.en
dc.contributor.authorBrady, A. F.en
dc.contributor.authorBlankenstein, O.en
dc.contributor.authorProcter, A. M.en
dc.contributor.authorDimitri, P.en
dc.contributor.authorWales, J. K. H.en
dc.contributor.authorGhirri, P.en
dc.contributor.authorKnÖBl, D.en
dc.contributor.authorStrahm, B.en
dc.contributor.authorErlacher, M.en
dc.date.accessioned2022-11-07T23:32:34Z-
dc.date.available2022-11-07T23:32:34Z-
dc.date.issued2017en
dc.identifier.citation99 , 2017en
dc.identifier.otherRISen
dc.identifier.urihttp://dora.health.qld.gov.au/qldresearchjspui/handle/1/2536-
dc.description.abstractIntrauterine growth restriction (IUGR) is a common condition that is sometimes associated with additional features, and in some cases endocrine dysfunction. We investigated eight children who had IUGR together with a complex multisystem disorder involving gonadal, adrenal and bone marrow failure. Several children died in the first 2 years of life. Using NGS and targeted capture, heterozygous de novo missense mutations in SAMD9 (chr 7q21•2) were identified in all eight children. SAMD9 was shown to be a growth repressor and these mutations result in gain-of-function, leading to reduced cell proliferation. Furthermore, progressive loss of the mutated gene through the development of monosomy 7 (-7), deletions of 7q (7q-) and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth restricting effects of the mutant proteins in bone marrow and was associated with increased length of survival. However, two patients with-7/-7q developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.1 genes. These findings provide strong evidence that dynamic somatic changes can occur in specific tissues. These changes can modify disease phenotype and influence survival. Tissue-specific adaptability such as this may be an under-recognised mechanism modifying the phenotype of human genetic.L6195234222017-12-08 <br />en
dc.language.isoenen
dc.relation.ispartofGenetics Researchen
dc.titleDeleterious growth restricting effects of human SAMD9 mutations are rescued by dynamic genomic changesen
dc.typeArticleen
dc.identifier.doi10.1017/S0016672317000039en
dc.subject.keywordschilden
dc.subject.keywordsfemaleen
dc.subject.keywordsframeshift mutationen
dc.subject.keywordsgene deletionen
dc.subject.keywordsgonaden
dc.subject.keywordshaploinsufficiencyen
dc.subject.keywordsheterozygosityen
dc.subject.keywordshumanen
dc.subject.keywordsintrauterine growth retardationen
dc.subject.keywordsloss of function mutationen
dc.subject.keywordsmaleen
dc.subject.keywordsmissense mutationen
dc.subject.keywordsmonosomy 7en
dc.subject.keywordsmyelodysplastic syndromeen
dc.subject.keywordsnonsense mutationen
dc.subject.keywordsphenotypeen
dc.subject.keywordsrepressor geneen
dc.subject.keywordssurvival timeen
dc.subject.keywordscase reporten
dc.subject.keywordsbone marrow depressionen
dc.subject.keywordsadrenal glanden
dc.subject.keywordsendogenous compoundmutant proteinen
dc.subject.keywordscell proliferationen
dc.relation.urlhttps://www.embase.com/search/results?subaction=viewrecord&id=L619523422&from=exporthttp://dx.doi.org/10.1017/S0016672317000039 |en
dc.identifier.risid2423en
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.languageiso639-1en-
item.openairetypeArticle-
item.grantfulltextnone-
item.fulltextNo Fulltext-
Appears in Sites:Children's Health Queensland Publications
Queensland Health Publications
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